Studies of acid aerosols in six cities and in a new multi-city
investigation: design issues.
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Speizer, Frank E. 1989. Studies of acid aerosols in six cities and in
a new multi-city investigation: design issues. Environmental Health
Perspectives 79: 61-67.
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doi:10.2307/3430530
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Environmental Health Perspectives
Vol. 79, pp. 61-67, 1989
Studies of Acid Aerosols in Six Cities
and in a New Multi-City Investigation.
Design Issues
by Frank E. Speizer*
Techniques for measuring acid aerosols in the ambient environment have been developed only
recently. As part of the on-going Harvard Study on the Health Effects of Sulfur Dioxide and
Respirable Particulates, we have developed monitoring equipment for acidic particles that can be
used in multiple field settings. Preliminary data suggest that these strong acid aerosol measurements
may correlate with respiratory symptoms more closely than similar measurements of particulate
matter less than 15 gim in size. These results have led to the beginning of a U.S.-Canadian
cooperative study to assess the chronic effects of acid aerosols on the health of North American
children. Communities are being selected on the basis of anticipated levels of H2SO4 in ambient air
along with predicted levels of ozone and nitrates. Each community will undergo a 1-year period of
every other day, 24-hr monitoring with newly developed monitoring equipment that will allow for
quantification of H+ ion concentrations, as well as for specific measures of ozone and acid fractions.
At the end of the 1-year period, while measurements are still being made, approximately 600
children aged 7 to 11 in each of up to 24 communities will be assessed with standardized
questionnaires completed by parents, and pulmonary function will be measured in the children while
in school. By estimating chronic exposure from the year-long measurement of acid aerosols and
consideration of specific criteria for selecting communities to study, we hope to minimize potential
confounding to allow us to assess the chronic impact of strong acid in the atnosphere on the
respiratory health of these children.
Introduction
The public and scientific debate over acid rain and
its precursors has focused on the ecological effects and
secondary health effects related to mobilization of toxic
metals. Far less concern has been shown for direct
human health effects, either acute or chronic, due to
acid aerosols (1). Oxidation of primary pollutants
(sulfur and nitrogen oxides) to acidic gases and
particles is clearly identified as the main source of these
agents. Whether existing control strategies could be
implemented without devastating economic implications is not clear. How successful partial controls would
be is unknown.
There are remarkably few data on the health impact
of either current or past exposures to acidic air pollution. Clearly, large scale air pollution disasters in the
middle of this century involved acid aerosols, as well as
primary pollutants such as sulfur dioxide (SO2) and
smoke. From what has subsequently been learned
about the acute effects of SO2, it is very likely that the
*Department of Environmental Science and Physiology, Harvard
School of Public Health, 665 Huntington Avenue, Boston, MA 02115.
offending agent in those episodes was the particulate
matter. The acidity of those particles could have played
a major role, particularly in individuals with compromised cardiopulmonary systems.
Fortunately, it is not likely that levels of exposure resulting in the episodes identified from the 1940s to the
1960s will occur again in North America. However, it
is unknown whether less severe daily or cumulative
exposures to acid aerosols and gases can affect respiratory symptoms either by themselves or in conjunction
with other pollutants. Animal and clinical studies in
relatively small groups of subjects suggest the possibility of such adverse effects at sulfuric acid concentrations of 100 ,ug/m3 (2-5). Whether entire populations or only sensitive groups are affected is not
known.
Although epidemiologic studies suggest that groups
of free-living individuals may be affected by air pollution in general, there are no population-based studies
that have directly measured acid aerosol exposure and
response. Part of the problem has been the lack of an
operational monitoring system for measurement of
gaseous and aerosol acidity in ambient air. Mass of
size-fractionated particles (PM10 or PM2.5), SO2 or
62
F E. SPEIZER
nitrogen dioxide (NO2), and total particulate sulfate
(TS04), coupled with recent measures of acidic rain
water, have been presumed to represent surrogates for
acid aerosols, in the absence of a suitable method for
direct measurement of airborne acidity.
Although natural sources of these pollutants exist,
their primary origin in the eastern half of North
America is sulfur and nitrogen oxides released into
the atmosphere from point sources and oxidized during airborne transport to sulfuric and nitric acids.
Nitrogen oxides primarily come from transportation
and electric utilities. Sulfur oxides result from industrial processes and coal- and oil-fired power plants.
Assumed emission patterns, climatic wind patterns
(6), and the distribution of acid precipitation (7) suggest that elevated acid aerosol concentrations would be
expected from the upper Ohio Valley region on into
Southern Ontario. These findings led Bates and Sizto
(8,9) to evaluate hospital admission rates for respiratory conditions in Southern Ontario. No direct acid
aerosol measurements were made in these studies.
In another study of respiratory symptoms in a population of 5500 women from a rural area of Western
Pennsylvania, respiratory symptoms were associated
with levels of SO2 (10). Again, no direct measures of
acid were available; however, air mass trajectories for
this rural setting were suggestive of transport of acid
aerosols into this region.
In this report we present one of the health findings
in children from the Harvard Study of Air Pollution
and Health (Six-Cities Study) and suggest how that
result might be modified by the available acid data. We
will then discuss the direction of some of the analyses
currently underway to assess the effect of acid aerosols
on daily symptoms. We will spend the bulk of the discussion on the design issue of a newly initiated study
planned to assess directly the respiratory health impact
of acid aerosols in North American children.
Six-Cities Study
As part of the Six-Cities Study we recognized the
need to develop technology for measuring particulate
and gaseous H+ concentrations in the field setting.
Samplers and analytic methods for aerosol strong
acidity have been developed and are being used in the
Six-Cities Study (11).
Preliminary data indicate that although sulfate
levels were only slightly higher in Kingston-Harriman, 73.6 nmole/m3, than in St. Louis, 61.6 nmole/
m3, during 1985-1986. The mean of H+ ion concentrations actually determined was in fact higher in
Kingston-Harriman, 36.1 nmole/m3, than in St.
Louis, 10.3 nmole/m3 (Fig. 1). Spengler et al. describe
results from four of the six cities (12).
95%
75%
200 -
*
mean
1
50%
T
175 -
25%
I5%
150 -
12 5-
@
0
C
100
a
1
25
T
0
H+
St.Louis, MO
Kinigston,
TN
FIGURE 1. Distribution of sulfate (So2-) and hydrogen ion (H+) concentration in St. Louis, MO, and Harriman, TN. Reprinted with permission (11) .
63
STUDIES OF ACID AEROSOLS AND HEALTH
In a recent presentation of results for the 1980-1981
school year for children aged 7 to 11 years old, we
summarized the incidence of bronchitis in the previous year reported by parents (13). These results,
adjusted for age, were graphed by city against the
inhaled particulate (PM15) average level measured
over the 12 months prior to the time the child was seen
(Fig. 2). It is noteworthy that the prevalence of reported
bronchitis in Kingston is higher than would be
expected given the level of PM15 (Fig. 2). In many
comparisons between cities (13,14), Kingston has
higher than expected frequencies of respiratory symptoms. Lippmann (15) has suggested that this excess
may be due to higher aerosol acidity levels in Tennessee than in the other cities. In fact, mean H+ concentrations presented earlier were higher in Kingston
than any of the other three cities (12).
No direct aerosol acidity measurements were made
during or before the 1980-1981 school year, when these
children were examined. If these city-specific prevalences of bronchitis are replotted against mean H+ concentrations for four cities presented earlier by Spengler
(12), there is a relative shift in the ordering of the cities
(Fig. 3), which suggests a better correlation of bronchitis prevalence with H+ than with PM15.
Currently in the Six-Cities Study, acid measurements are being made in each of the cities for a 1-year
period. In conjunction with these measurements, daily
respiratory symptoms of approximately 300 children
in each city are being monitored using a diary technique supplemented by biweekly telephone contact (16).
To date, data collection has been completed in five cities,
and these data are currently being analyzed using
K
Un
'-i
'-4
I
z
0
tr
m
111
Lu
S
8-
7.6-
z
Lui
-J
LL
a:
Cl
54-
p
be
3.
2r- 10
10
2.
20
30
4
5
60
40
50
60
PM 15
FIGURE 2. Bronchitis in the last year, children 10 to 12 years of age in
six U.S. cities, by PM15. P = Portage, WI; T = Topeka, KS;
W = Watertown, MA; K = Kingston, TN; L = St. Louis, MO;
S = Steubenville, OH.
K
10
9.
(In
H-
S
8
'-4
H
-)7
z
0
7'-
uJ
6-
a:m
L
z
-J
5
LL
aR
4
P
3
2-
0
10
20
30
HI (nmoles/m3)
40
FIGURE 3. Bronchitis in the last year, children 10 to 12 years of age in
four U.S. cities by hydrogen ion concentrations. See Fig. 2 for
abbreviations.
Markov (17) and random effects (18) models of the
serial observations. Such analyses should provide
powerful data to assess the acute effects of acid aerosols
on symptom frequency in these children.
Multi-City Acid Aerosol Study
To directly assess the chronic effects of acid aerosols
on the respiratory health of children, we have proposed
a multi-city study in collaboration with investigators
from the Long Range Transport of Air Pollutants
(LRTAP) Health Effects section of Health and Welfare,
Canada. The study has just begun, and there are a
number of design issues that are currently under
review. One issue we would like to discuss relates to
criteria for site selection.
The plan of our study is first to characterize exposure
by collecting detailed acid aerosol measurements along
with measurements of SO2, NO2, and ozone (03) for a
1-year period prior to carrying out a health survey on
children aged 7 to 11 in the area. The aerometric
measures will be based on 24-hr recordings taken every
other day for a full year, with particular care in
obtaining 12-hr samples over the summer months
when acid events are predicted to be more frequent.
These measures will then be used as surrogates for
estimating chronic exposure defined as both level and
frequency of excursions over specific defined acid
aerosol levels for the lives of the children in the study.
After a 1-year period of collection of environmental
data, children from the chosen communities, selected
by school districts, will be visited in their schools. The
64
F E. SPEIZER
project will be explained to them and they will be asked
to take home a questionnaire to their parents to provide
information about the home environment, the child's
past medical history, current symptomatology, demography of the household, and smoking habits and
disease frequency of the parents. Much of this information has been gathered for several years in a
standardized fashion using the Six-Cities Study
modification of the ATS/DLD children's questionnaire (19). Finally, the parent will be asked to sign a
permission slip allowing us to examine the child in
school.
Upon return of the completed questionnaire to the
school and review for completion by our staff, a
scheduled visit to the school will be made by our field
team. At this visit each child will undergo spirometry
in a standardized manner. While seated in a comfortable chair, with noseclip in place, the child will
breath tidally on a dry rolling seal spirometer (Morgan Company, Andover, MA). At the end of a normal
inspiration, the child will be asked to breath out as
hard and fast as he/she can to residual volume (RV).
This will be followed by a maximal inspiration to total
lung capacity followed by another forced expiratory
maneuver to RV. Both the partial and the entire flow
volume curve will be recorded. The procedure will be
repeated to obtain three acceptable tracings using AIS
standard criteria (19). All volumes will be converted to
body temperature and pressure, saturated (BTPS). The
child's height and weight in stocking feet will be
measured.
These forced partial and maximal expiratory maneuvers will be used to derive a series of measures on
each child that characterize the pulmonary function
status of the child in terms of normal growth, airway
size, and, potentially, airway tone. To the degree that
the information gathered from the parent can be used
to adjust for potential confounding or risk modifying
factors, the difference seen between children from
different communities can be associated with differences in levels of exposure to ambient levels of acid
aerosol exposures.
How we get from the data collection to this last test of
association is not so trivial and is worth spending
some time discussing. The basic design of the study
was suggested to us by Professor John Tukey, who was
one of our advisors on the Six-Cities Study. In that
study, we were faced in all of our regression analyses
with the phenomenon that our point estimates for each
city were quite good, with each estimate usually based
on more than 1000 observations. However, when we
combined the data across six communities and tried to
use the exposure data in a continuous manner, our
true sample size often fell to something more like 6
rather than 6000. Thus, all of our cross-sectional
analyses in the Six-Cities Study that try to assess the
effect of the ambient exposure gradient across the six
communities suffer from a lack of statistical power.
Only because the study has been longitudinal, with
repeated measures on the same children, and the fact
that exposure levels have been changing can we make
definitive statements about the results. We have taken
this phenomenon into account in the design of the
new study.
The new study can be considered prospective from
the perspective that the aerometric measures (exposure)
precede the measure of respiratory symptoms and
pulmonary function (effects). However, in terms of
formal design (and significantly affecting cost) the
study must be considered as a prevalence cross-sectional study rather than an incidence (i.e., longitudinal) study. The subjects are to be seen at only one
point in time. We are postulating that their cumulative life events will be manifest in their histories and
pulmonary function levels at least for those that are
lifelong residents of their individual communities. If
we can control for those important known risk factors
and can demonstrate a difference between children
from communities with and without significant acid
aerosol pollution, we may be able to conclude that these
differences are associated with not only the levels found
in the previous monitored year but also that the
ambient measures recorded are likely to reflect what
has been occurring over the 7- to 10-year life span of the
children.
Our objective in studying groups of children is to
maximize the differences in exposure levels to construct an exposure-response relationship and at the
same time to minimize the variance of any single
point estimate about the line that summarizes the
exposure-effect relation. Data available from the SixCities Study were used to estimate the level of difference
we might expect in symptom frequency among groups
of exposed and unexposed children. With this information we calculated the sample size necessary to have
sufficient power to have a chance of finding a difference if one was present. Given approximately an 8 to
15% occurrence of most symptoms in the unexposed
groups, to detect a 40% increase in risk of any given
symptom, with sample series of 600 children in each
community, by studying 24 communities our power
to detect such an increase in risk is between 0.74 and
0.92. This estimate also takes into account the expected
between town variances.
Thus, our plan is to enter three sets of eight sites over
3 years into the study. In each site we anticipate seeing
more than 700 children to have approximately 600
lifelong residents of the community in the study. In
contrast to the 40% excess risk to be detected for symptoms, for pulmonary function measures similar calculations suggest that we should be able to detect
approximately a 0.5 to 3.0% difference in lung function
level. Given that the magnitude of the passive smoking
effect in children is in the range of 1% for the age group
we will be studying (20) and the fact that colleagues
from Canada were able to detect a 2% difference in lung
function level between two groups of five communities
(21), we believe that the power to detect significant
difference in lung function is both sufficient and
potentially of biologic importance. Time does not
65
STUDIES OF ACID AEROSOLS AND HEALTH
permit me to fully justify this statement here, and
interested readers should see indicated references on
the natural history of the development of chronic
obstructive pulmonary disease (COPD) (22-24).
To maximize our chances to find significant
differences between communities at different levels of
exposure we must deal with the anticipated chemistry.
From the few studies that have attempted to monitor
acid, it is clear that at least two distinct sources can be
identified. We know that downwind from urban areas
with major transportation sources, significant levels of
nitric oxides and acid may occur. In addition acid
aerosols result from long-range transport of pollutants
generated from the combustion of fossil fuels (SO2 and
particulates), which are converted in the atmosphere to
sulfuric acid. To the degree that this might occur
independently of NOx downwind from metropolitan
areas, it would appear to relate to the height to which
the emissions are dispersed and to the distance in the
atmosphere the air masses have traveled before
affecting a distant region or being precipitated out as
acid rain. In each case, at least in the summer because
of reactions in the sunlight, these major classes of
different acids may occur in conjunction with or
separate from elevated levels of 03. In winter, the pollutants most likely to accumulate in the atmosphere are
the sulfur oxides. Recent studies have suggested that
03 may act independently of acid components in the
air to affect respiratory symptoms (25) and, at least
acutely, level of pulmonary function (26). Thus, the
problem in studying the chronic effects of acid aerosols
is to identify sites in which differences in levels of
exposures to ozone, sulfates, and nitrates can be found.
Thus, in selecting sites, we must identify three replicates that meet the criteria indicated in Table 1. This
would provide the most efficient design and allow us to
test each pollutant separately and in combination with
each other. We need, therefore, to define what is meant
by high and low for each pollutant. Table 2 is one of our
preliminary attempts at doing this and points out the
ranges that we believe can be studied.
The pollution level is only one criteria, albeit a
critical one, in defining potential study sites. We also
must consider the demography of the site. Table 3
summarizes the criteria that must be set for an area to
be considered acceptable. We found that we would be
forced to restrict on race to avoid the potential confounding of the interaction of city and race. Similarly,
Table 1. Replicates for site selection.
03
High
High
Low
Low
High
High
Low
Low
H2SO4
High
High
High
High
Low
Low
Low
Low
HNO3
High
Low
High
Low
High
Low
High
Low
Table 2. Ranges of annual mean and maximum pollution levels for
high/low classification of exposure.
03,
SO47
Sampling period ppb/hr Pg/Mm3/day
High
> lOOa
> 30
Maximum
> 50b
> 12
Mean
Low
< 80a
< 20
Maximum
< 30b
<3
Mean
al-hr maximum.
b7-hr mean (May-September).
NO3,
Pg/m3/day
H2SO4,
,g/m3/day
> 10
>5
> 15
>3
<3
< 1
< 10
< 1
Table 3. Demographic characteristics for communities to be included
in Multi-City Acid Aerosol Study.
Population
Race
Family income
Stability
Cooking fuel
At least 2000 white families with children under
18 years of age
At least 85% of the total population should be
white
No more than 5% of all families with children
under 18 years of age should have a family income
below the poverty level
At least 70% of the residents over 5 years of age
should have lived in the same county for the past
5 years
The proportion of housing units using electricity
as their cooking fuel should be between 15 and 85%
we wanted social class (with family income as a
surrogate) to be relatively homogeneous and wanted to
avoid a major difference in indoor sources (i.e.,
cooking fuels) as a potential confounder.
In an attempt to be in the field within the first 2
months of the study, we decided to select the first four
sites, such that in addition to meeting the criteria
defined previously, the sites would also be close to a
monitoring site in the U.S. and Canadian acid rain
network run jointly by the U.S. Environmental Protection Agency, the Electric Power Research Institute,
the Canadian Atmospheric and Environment Service,
and the Ontario Ministry of the Environment. These
network sites have been established to evaluate models
of acid rain deposition. These sites should all be operating beginning in the fall-winter of 1987. Table 4 identified these sites in the categories corresponding to our
best estimates of what will be measured as to level of 03,
(H2SO4), or (HNO3). From these selected sites field personnel will visit the area to determine suitability, and
this large multidisciplinary effort will be underway.
For this effort to be successful will take not only a
large effort by a committed and technically competent
staff, but also a very significant degree of cooperation
from local health departments and school boards,
children, and their parents. We hope that if another
workshop on acid aerosols is organized for 3 years
from now, we will be able to return to present at least
part of the results of this endeavour.
F E. SPEIZER
66
Table 4. Preliminary sites selected for Multi-City Study.
03
High
H+
SO2
High
High
High
Low
High
Low
High
High
Low
High
Low
Low
Low
Low
Low
Experimental design categories
of pollution characteristics
High North Central/urban complex 20-80 km
New York City suburbs
Southwestern Connecticut
Pittsburgh suburbs
Southeastern Pennsylvania
Central New Jersey
Southern Ontario
St. Louis suburbs
Ohio
Northern West Virginia
Maryland
Northern Virginia
Delaware
Low North Central/urban complex > 100 km
Upstate New York
Kentucky
West Virginia
Virginia
Indiana
Southern Illinois
High Northern/urban complex 20-80 km
New England
Northern Illinois
Southern Michigan
Low Local sources-acid plants/smelters
High Southern/urban complex 20-80 km
Southern Texas
Southern Louisiana
Mississippi
Southern California
Low Southern/urban complex > 100 km
Southern Florida
Central California
High Northern/urban complex 20-80 km
Northern California
Southern Oregon
Low Baseline pollution level
Northern Wisconsin
Minnesota
Montana
North Dakota
Manitoba
Saskatchewan
Western Ontario
H+
NO,
Supported in part by National Institute of Environmental Health
Sciences grants ES-04595, ES-01108 and ES-0002, Environmental
Protection Agency Cooperative Agreement CR-811650 and Electric
Power Research Institute Contract RP-1001. This report has not been
subjected to the Environmental Protection Agency's required peer and
policy review and therefore does not necessarily reflect the views of the
Agency, and no official endorsement should be inferred. F E. Speizer
represents the following investigators from the Harvard School of
Public Health and the Harvard Medical School: D. Dockery, B. Ferris,
G. Keeler, P. Koutrakis, L. Neas, J. Spengler, J. Ware, R. Burnett, C.
Franklin, M. Raizenne, and B. Stern and from Health and Welfare,
Canada.
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